Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.26 (
GSK
)
6,788
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glycogen synthase kinase 3beta (
GSK
3 beta) is a serine/ threonine kinase that phosphorylates substrates such as beta-catenin and is involved in a variety of biological processes, including embryonic development, metabolism, tumorigenesis, and cell death. Here, we present evidence that human
GSK
3beta is associated with Fe65, which has the characteristics of an adaptor protein, possessing a WW domain, and two phosphotyrosine interaction domains,
PID1
and PID2. The
GSK
3beta catalytic domain also contains a putative WW domain binding motif ((371)PPLA(374)), and we observed, using a pull down approach and co-immuno-precipitation, that it interacts physically with Fe65 via this motif. In addition, we detected co-localization of
GSK
3beta and Fe65 by confocal microscopy, and this co-localization was disrupted by mutation of the putative WW domain binding motif of
GSK
3beta.Finally, in transient transfection assays interaction of
GSK
3 beta (wt) with Fe65 induced substantial cell apoptosis, whereas interaction with the
GSK
3beta AALA mutant ((371)AALA(374)) did not, and we noted that phosphorylation of the Tyr 216 residue of the
GSK
3beta AALA mutant was significantly reduced compared to that of
GSK
3beta wild type. Thus, our observations indicate that
GSK
3beta binds to Fe65 through its (371)PPLA(374) motif and that this interaction regulates apoptosis and phosphorylation of Tyr 216 of
GSK
3beta.
...
PMID:The PPLA motif of glycogen synthase kinase 3beta is required for interaction with Fe65. 1854 80
